The present invention relates to a method and apparatus for hyperpolarizing a gas sample. In particular, the present invention relates to hyperpolarizing a noble gas for use in MRI and NMR experiments.
Conventional MRI techniques exploit the interaction of the intrinsic magnetic moment or spin of nuclei with an applied magnetic field. Nuclei whose spin is aligned with the applied magnetic field have a different energy state to nuclei whose spin is aligned opposed to the applied magnetic field. Accordingly, by applying a radio frequency radiation to the nuclei in a magnetic field, nuclei can be made to jump from a lower energy state to a higher energy state. The signals produced when the nuclei return to the lower energy state can then be measured, thereby providing information concerning the nature of the physical properties of the object being measured.
In most cases, MRI and NMR imaging is carried out using hydrogen nuclei which are present in water and fat. However, suitable nuclei are not always naturally present to enable measurements to be made. Thus, for example, in the lungs there are too few protons to generate a clear image. In addition to this microscopic air/tissue interfaces of the lung produce magnetic field variations that cause the already weak signal to decay even more rapidly. The problem is further exasperated by normal breathing and cardial motion.
A proposed solution to this is for the patient to inhale a mixture of a buffer gas, such as Nitrogen or Helium, and a strongly polarised sample gas, such as a noble gas. The hyperpolarized noble gas, as it is known, is a gas which includes an induced polarization, and hence an induced magnetic moment in the atomic nuclei. This allows MRI and NMR experiments to be performed in the normal way, even if the normally used hydrogen nuclei are not present.
Currently there are two main techniques for generating hyperpolarized gases. The first technique is described for example in U.S. Pat. No. 5,809,801, U.S. Pat. No. 5,617,860 and U.S. Pat. No. 5,642,625.
The technique described in these documents is the indirect hyperpolarization of Xenon or Helium3 (3He). This is achieved by mixing the gas with a small amount of an alkaline-metal vapour, such as rubidium. A weak magnetic field is applied to the vapour mixture to cause splitting of the alkaline-metal electron energy levels.
The vapour mixture is then optically pumped using a laser to cause a build-up of electron polarization in the higher energy sub-level of the metal vapour. Nuclei of the noble gas atoms then become polarized by collisions with the alkaline-metal which causes transfer of angular momentum from the polarized alkali electrons to the nuclei spin of the noble gas.
An alternative method of hyperpolarizing 3He is achieved by direct optical pumping of a metastable state of the helium. In this method an electrical discharge and a low pressure cell are used to create atoms of 3He in a metastable state. These metastable atoms are then exposed to circularly polarized laser light, from a high powered LNA-laser, which causes the transfer of polarization from the electrons to the helium nuclei via coupling with the unpaired neutron.
Both of the above mentioned methods rely on optical pumping techniques and are therefore extremely inefficient.
Other methods have been considered which involve the use of solidified Xenon. However, the Xenon has a long spin-lattice relaxation time and therefore must be kept in a strong magnetic field, at a low temperature, for long periods of time to result in any useful level of polarization. This direct approach is therefore impractical.
In order to overcome this, the document xe2x80x9cHigh Equilibrium Spin-Polarizations in Solid 129Xenonxe2x80x9d by Honig et al, proposes mixing the Xenon with bulk amounts of oxygen to help improve the polarization. Meanwhile xe2x80x9cThe Brute Force 129Xe and D2 Polarization at low temperaturexe2x80x9d by Usenko et al describes achieving polarization by inducing an electron current in the solidified Xenon. Again however, these techniques have proved to be extremely inefficient.
FROSSATI G: xe2x80x9cPolarisation of He, D2 (and possibly Xe) using cryogenic techniquesxe2x80x9d NUCLEAR INSTRUMENTS and METHODS IN PHYSICS RESEARCH, SECTIONxe2x80x94A: ACCELERATORS, SPECTROMETERS, DETECTORS AND ASSOCIATED EQUIPMENT, NORTH-HOLLAND PUBLISHING COMPANY AMSTERDAM, NL, vol. 402, no. 2-3, Jan. 11, 1998, pages 479-483 discloses a method of hyperpolarizing a gas sample, the method comprising the steps of cryogenically forming a solidified gas structure from the sample gas, the solidified gas structure being surrounded by 3He, applying a magnetic field to the solidified gas structure and the 3He to thereby polarize the solidified gas structure, and removing the 3He to thereby leave a solidified gas structure of hyperpolarized sample gas.
In accordance with a first aspect of the present invention, we provide a method of hyperpolarizing a gas sample, the method comprising the steps of:
a. cryogenically forming a solidified gas structure from the sample gas, the solidified gas structure being surrounded by 3He;
b. applying a magnetic field to the solidified gas structure and the 3He to thereby polarize the solidified gas structure; and
c. removing the 3He to thereby leave a solidified gas structure of hyperpolarized sample gas, characterized in that step (c) comprises the steps of:
i. increasing the temperature of the solidified gas structure;
ii. introducing 4He into the region surrounding the solidified gas structure to thereby displace the 3He; and
iii. pumping the 3He and the 4He away from the solidified gas structure.
In accordance with a second aspect of the present invention, we provide apparatus for hyperpolarizing a gas sample, the apparatus comprising:
a. cryogenic apparatus for forming a solidified gas structure from the sample gas, the solidified gas structure being surrounded by 3He;
b. magnetic field generating assembly for applying a magnetic field to the solidified gas structure and the 3He to thereby polarize the 3He and the solidified gas structure; and
c. a removal system for removing the 3He to thereby leave a solidified gas structure of hyperpolarized noble gas, characterized in that the removal system is adapted to carry out the steps of:
i. increasing the temperature of the solidified gas structure;
ii. introducing 4He into the region surrounding the solidified gas structure to thereby displace the 3He; and
iii. pumping the 3He and the 4He away from the solidified gas structure.
Accordingly, the present invention provides a method and an apparatus for producing a hyperpolarized sample gas. In this technique, a solidified gas structure is formed which is surrounded by 3He. A magnetic field is then applied to the gas structure and the 3He which causes polarization of the solidified gas structure. Under conditions of low temperature, solidified gases normally have an extremely low relaxation rate. However, in the present invention magnetic dipolexe2x80x94dipole coupling at the gas structure/3He interface leads to an increase in the relaxation rate of the solidified gas, thereby increasing the rate at which the solidified gas is polarized. The 3He is then removed to leave behind a solidified gas structure of hyperpolarized noble gas. This can then be used in NMR and MRI experiments as required.
The step of cryogenically forming a solidified gas structure surrounded by 3He usually comprises the steps of forming a solidified gas structure and, introducing the 3He into the regions surrounding the solidified gas structure. Alternatively however the solidified gas structure is formed in an environment including 3He.
Typically the step of forming a solidified gas structure comprises the step of cooling a substrate within a chamber and, introducing the sample gas into the chamber thereby causing the sample gas to condense onto the substrate. However, alternatively the gas structure may be formed by introducing the sample gas into an environment including a substrate and then cooling the entire environment to cause the sample gas to condense onto the substrate.
Typically the introduction of the sample gas into the chamber is controlled such that the sample gas condenses to form a solidified gas layer on the substrate, the layer having a thickness of about 10 monolayers. This is particularly advantageous as the increased relaxation rate induced by the 3He is only effective for the uppermost layers of the solidified sample gas structure. Layers of the solidified gas further from the 3He will become polarized by spin diffusion effects which take time to propagate through the sample. For layers polarized by this technique, the effect of the 3He on the relaxation rate is reduced and it is therefore preferable to ensure that as much of the solidified gas structure as possible is in contact with the 3He to thereby ensure as high a relaxation rate as possible. However, thicker layers of noble gas may be used if the 3He is maintained in contact with the noble gas for longer periods of time.
It is preferable that the substrate is a porous medium so as to ensure the formation of a gas structure with a high surface area. Furthermore, it is preferable to ensure a low concentration of paramagnetic contaminants. Accordingly, the substrate is typically a fumed silica. However, any suitable substance having a high surface area could be used, such as activated carbon, exfoliated graphite, clays, porous glasses, zeolites, silica areogels, and silicas may also be used.
The solidified gas structure is preferably porous and has a large surface area. This ensures that as much of the noble gas as possible can be condensed and then polarized whilst interacting with the 3He thereby ensuring the polarization times are kept to a minimum. However, a reduced surface area could be used if other parameters such as the temperature of the substrate and the applied magnetic field are adjusted accordingly.
Typically the step of introducing the 3He into the region surrounding the solidified gas structure comprises precooling the solidified gas structure and, immersing the precooled solidified gas structure in liquid 3He. In this case, because the gas structure has a low heat capacity, it can be cooled to a temperature of below 4.2K and then immersed in the liquid 3He without causing an undue temperature rise in the 3He, which is itself typically cooled to a temperature of less than 100 mK and preferably to a temperature of 10 mK. This technique also ensures the entire surface of the solidified gas structure will be in contact with the 3He to ensure adequate bonding occurs. Furthermore, this allows the 3He to be maintained at a low temperature (below 100 mK) thereby overcoming the need to repeatedly cool the 3He.
However, the introduction of 3He into the area surrounding the gas structure may alternatively involve the steps of introducing the 3He into a chamber containing the solidified gas structure so as to fill the pores of the solidified gas structure and cooling the solidified gas structure to cause a 3He to solidify on the surface of the solidified gas structure. A further alternative is for the solidified gas structure may be precooled so that the 3He condenses and solidifies as soon as it has entered the chamber.
The method preferably further comprises cooling the solidified gas structure and the 3He to a temperature of less than 100 mK. In this case, the magnetic field applied to the solidified gas structure and the 3He has a strength of between 10 and 20T. However, alternative values of temperature and magnetic field can be used by adjusting other parameters to compensate for any reduction in the induced polarization. Thus for example, if a reduced magnetic field is used, the magnetic field could be applied for a longer periods of time. Ultimately however, the level of polarization will depend on the applied field and the inverse of temperature. It is therefore preferable to use as large a field as possible at a low temperature.
Typically the sample gas is a noble gas sample which comprises 129Xe. However, any suitable sample gas such as 131Xe, 83Kr 39Ar, 21Ne, 15N, 2D or the like, could be used. Accordingly, this does not represent an exhaustive list of the samples which can be polarised using the technique of the present invention.
Alternatively however, the sample gas could comprise 3He in which case, the 3He is preferably formed as a layer of solid on a substrate, with the solidified gas structure being surrounded by liquid 3He. This therefore allows hyperpolarized helium to be produced by the techniques of the present invention.
The method preferably further comprises the step of storing the hyperpolarized gas in the form of the solidified gas structure by maintaining the solidified gas structure in a magnetic field having a strength of between 50 mT and 1T at a temperature of below 10K. However, the gas may alternatively be vaporised and used immediately. The hyperpolarized gas can be obtained from the solidified gas structure by raising the temperature of the solidified gas structure to above 161K.
As previously described, the hyperpolarized gas is then suitable for use in NMR and MRI type analysis techniques. In the case of MRI, the hyperpolarized gas can be mixed with a buffer gas and then inhaled, allowing details of the lungs to be determined.
The cryogenic apparatus usually comprises a cell containing a porous substrate, the cell having an input for receiving the noble gas; a cooling system; and, a controller for controlling the cooling system, the controller being adapted to cause the cooling system to cool the cell thereby causing the noble gas to condense on the substrate so as to form a porous solidified gas structure.
Typically the removal system comprises a pump coupled to the cell, the controller operating to control the cooling system to raise the temperature of the cell so as to cause evaporation of the 3He, the pump being adapted to remove the 3He vapour from the cell. However, the controller could be adapted to raise the temperature of the cell to vaporise both the noble gas and the 3He. In this case, the apparatus would further comprise means for separating the resulting gas mixture.
Preferably the removal system further comprises a source of 4He, the source being coupled to the input to supply 4He into the cell, the 4He causing displacement of the 3He from the solidified gas structure. However, the removal of the 3He can be implemented without the addition of the 4He.
Typically the controller is also coupled to the magnetic field generating apparatus for controlling the magnetic field applied to the cell. This allows the applied field and the temperature of the solidified gas structure to be accurately controlled by a single element, thus ensuring that the solidified gas structure is subject to the ideal conditions for polarization.
The magnetic field generating apparatus will usually comprise at least one superconducting coil. However, several separate sets of coils may be used to ensure that fields of the desired strength and homogeneity can be generated for the entire solidified gas structure. As a result, the magnetic filed generating apparatus may also include permanent magnets.